Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene

August 2, 2023 updated by: Klus Pharma Inc.

A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies

Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, Phase I-II, first-in-human (FIH) study for A166 as monotherapy in HER2-expressing patients who progressed on or did not respond to available standard therapies. Patients enrolled in this Phase III study must have documented HER2 positivity defined as positive on in situ hybridization (ISH) or next-generation sequencing (NGS) or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease. Patients will receive study drug as a single IV infusion at the prescribed dose level in each treatment cycle. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Sarasota, Florida, United States, 34232
        • Florida Cancer Specialists & Research Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New York
      • Lake Success, New York, United States, 11042
        • Clinical Research Alliance, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Stephenson Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Cancer Institute
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research Centers - Medical City
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • South Texas Accelerated Research Therapeutics, LLC (START)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialist

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Phase I

Patients must meet the following criteria for inclusion into the study:

  1. Patients must be able to provide documented voluntary informed consent.
  2. Male or female patient ≥ 18 years.
  3. Histologically documented, incurable, locally advanced or metastatic cancer.
  4. Evaluable or measurable HER2 positive (by ISH or NGS) disease or HER2 expressing disease. HER2 expressing is defined in this protocol as HER2 expression of ≥ 1+ determined by validated IHC.
  5. Patients should have no available therapy likely to convey clinical benefit.
  6. Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL.
  7. Serum bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN), with the exception of patients with hepatic metastases (ALT and AST ≤ 5 × ULN) and patients with hepatic and/or bone metastases (alkaline phosphatase ≤ 5 × ULN).
  8. Creatinine clearance ≥ 50 mL/min calculated by Cockroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or Modification of Diet in Renal Disease (MDRD) formulas. Note that 24 hour urine collection is not required but is allowed.
  9. ECOG Performance Status ≤ 1.
  10. Women of childbearing potential and men must agree to use an approved method of birth control (e.g., hormonal, barrier) while receiving study drug, and for at least 7 months after the last dose of study drug. Women are excluded from birth control if they had had tubal ligation or a hysterectomy.
  11. Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia and vitiligo.

Exclusion Criteria:

Phase I:

  1. Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure (New York Heart Association) III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia).
  2. History of Grade ≥ 3 hypersensitivity reaction to trastuzumab.
  3. History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued.
  4. Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first infusion of study drug.
  5. Require supplemental oxygen for daily activities.
  6. Documented Grade ≥ 2 peripheral neuropathy.
  7. Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy treatment within 4 weeks of first infusion of study drug.
  8. Any experimental therapy within 4 weeks of first infusion of study drug.
  9. Any major surgical procedure within 4 weeks of first infusion of study drug.
  10. Diagnosed active liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis. Patients who have positive hepatitis B virus test results due to having been previously vaccinated against hepatitis B, as evidenced by negative hepatitis B surface antigen (HBsAg), negative anti hepatitis B core protein, and positive antibody to the HBsAg (anti-HBs) are not excluded.
  11. Have known prior positive test results for human immunodeficiency virus.
  12. Uncontrolled hypertension or diabetes.
  13. Pregnancy or lactation.
  14. Resting corrected QT interval (QTc) > 470 ms at baseline.
  15. Left ventricular ejection fraction (LVEF) < 45% determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  16. Prior cumulative doxorubicin dose of > 360 mg/m2 or equivalent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I: Dose Escalation
Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
Experimental: Phase II: • Cohort 1
HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
Experimental: Phase II: • Cohort 2
HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
Experimental: Phase II: • Cohort 3
HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.
Experimental: Phase II: • Cohort 4
All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose.
Drug: A166
A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Maximum Tolerated Dose
Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Number of patients with dose limiting toxicities
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase I: Number of patients with Dose Limiting Toxicities
Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time Frame: Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Every 3 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I: Number of participants who developed measurable anti-drug antibodies
Time Frame: Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Minimum of 21 days from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Phase I Maximum observed serum or plasma concentration (Cmax).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose
Phase I Clearance (CL).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose
Phase I Area under the serum or plasma concentration time curve from 0 to infinity (AUC[0-∞]).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose
Phase I Terminal phase elimination half life (t½).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose
Phase I Volume of distribution at terminal phase (Vz).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose
Phase I Volume of distribution at steady state (Vss).
Time Frame: 84 Days from date of first dose
84 Days from date of first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Klus Pharma Inc.

Investigators

  • Study Chair: Jordi Rodon Ahnert, MD, PhD, MD Anderson

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 16, 2018

Primary Completion (Actual)

January 12, 2022

Study Completion (Actual)

January 12, 2022

Study Registration Dates

First Submitted

July 6, 2018

First Submitted That Met QC Criteria

July 25, 2018

First Posted (Actual)

July 26, 2018

Study Record Updates

Last Update Posted (Actual)

August 3, 2023

Last Update Submitted That Met QC Criteria

August 2, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KlusPharma

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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